Methods, compositions and articles of manufacture for contributing to the treatment of solid tumors

a technology of compositions and articles, applied in the field of methods, compositions and articles of manufacture for contributing to the can solve the problems of unfulfilled medical goals, selective, unfavorable treatment of solid tumors, etc., and achieve the effect of effective delivery of chemotherapeutic agents and enhanced treatmen

Active Publication Date: 2006-09-21
THE BOARD OF TRUSTEES OF THE UNIV OF ILLINOIS
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0009] The present invention is directed to the administration of endothelin agonists and a chemotherapeutic agent to an individual in need thereof to contribute to the treatment of a solid tumor. In particular, tumors have distinctive vasculature including an increased number of ETB receptors which, when bound, cause vaso

Problems solved by technology

Successful treatment of solid tumors, including breast cancers, remains an unfulfilled medical goal, despite increased understanding of the molecular biology of tumor cells and the availability of an increased number of potential therapeutic agents.
One problem in the treatment of cancers is that an effective dose of a wide variety of potential chemotherapeutic agents is restricted by these agents' non-selective, highly

Method used

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  • Methods, compositions and articles of manufacture for contributing to the treatment of solid tumors
  • Methods, compositions and articles of manufacture for contributing to the treatment of solid tumors
  • Methods, compositions and articles of manufacture for contributing to the treatment of solid tumors

Examples

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Effect test

example 1

Effect of IRL1620 and Paclitaxel on Breast Tumor Perfusion Methods

[0052] The following studies were conducted to examine the systemic hemodynamics and regional circuitry effects of ET-1 in normal and breast tumor-bearing rats.

[0053] One extensively studied breast tumor model is the chemically induced rat mammary carcinogenesis model. van Zwieten, The rat as animal model in breast cancer research. Martinus Nijhoff Publishers, Boston, pg. 206 (1984); Dao et al., J Natl Cancer Inst, 71:201 (1983); Russo et al., J Natl Cancer Inst, 61:1439 (1978). Huggins et al., Science, 137 (1962); Huggins et al., Proc Natl Acad Sci USA, 45:1294 (1959). Chemically induced mammary tumorigenesis in rats is the model most closely resembling a human cancer. Russo et al., Lab Invest, 62:244 (1990). In terms of tissue architecture, the mammary gland of a rat is comparable to that of human women. It is formed by an epithelium that covers the ducts and alveoli and a stroma, the connective tissue scaffolding...

example 2

Effect of ET-1 Infusion on Systemic Hemodynamics and Blood Flow to the Mammary Tissue of Normal and Tumor-bearing Rats

Methods

[0066] MNU and saline treatments were performed as i.p. injections three months prior to the study. Rats were palpated regularly starting four weeks after the treatments. Once tumors reached 4-8 mm in diameter, the experiments were initiated.

[0067] Rats were anesthetized with urethane (1.5 g / kg, i.p.) (Sigma Chemicals, St. Louis, Mo.). All surgical areas were shaved and cleaned with alcohol swabs. The left femoral vein was cannulated (PE 50 tubing, Clay Adams, Parsipanny, N.J.) for drug administration. The left femoral artery was cannulated (PE 50 tubing) and was used for withdrawal of reference blood sample in microsphere studies using a withdrawal pump (Model 22, Harvard Apparatus, South Natick, Mass.). The right femoral artery was cannulated (PE 50 tubing) and connected to a Gould P23 ID pressure transducer for recording the blood pressure on a Grass P7...

example 3

Effect of IRL1620 on Tumor Blood Perfusion and Chemotherapeutic Agent Delivery

[0090] Previous experiments demonstrated that administration of ET-1 to breast tumor bearing rats increased blood flow selectively to tumor tissue by stimulating ETB receptors. The experiment described in this example will be conducted to determine the effect of the ETB receptor agonist, IRL1620 on breast and melanoma tumor perfusion and its effect on paclitaxel accumulation in tumor and other major organs.

Methods

[0091] Breast tumors will be induced in virgin female Sprague Dawley rats (48 days of age) by N-methyl nitrosourea (MNU; 50 mg / kg, i.p.). Rats with a tumor volume of 300-500 mm3 will be anesthetized with urethane (1.5 g / kg i.p.) and treated with saline (0.3 ml / kg, i.v.) or IRL1620 (3 nmol / kg, i.v) as described previously. Tumor perfusion will be measured for 10 h using a Periflux PF2b 4000 Laser Doppler Flowmetry as described previously. In a second study, nude mice will be subcutaneously inoc...

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Abstract

Methods, compositions and articles of manufacture for contributing to the treatment of a solid cancerous tumor are disclosed. The methods, compositions and articles of manufacture can utilize an endothelin B agonist (ETB) to enhance the delivery of a chemotherapeutic agent to a solid tumor in mammals, including humans.

Description

CROSS-REFERENCE TO RELATED APPLICATION [0001] This application is a continuation-in-part of U.S. patent application Ser. No. 10 / 691,915 filed Oct. 23, 2003 which claims the benefit of U.S. provisional patent application No. 60 / 420,960, filed Oct. 24, 2002, U.S. provisional patent application No. 60 / 655,656, U.S. provisional patent application No. 60 / 655,654, and U.S. provisional patent application No. 60 / 655,643 all three filed on Feb. 22, 2005, the entire disclosure of which is incorporated herein by reference.FIELD OF THE INVENTION [0002] The present invention relates to methods, compositions and articles of manufacture for contributing to the treatment of solid tumors, such as breast tumors, in a mammal, through administration of an endothelin agonist and a chemotherapeutic agent. BACKGROUND OF THE INVENTION [0003] Breast cancer incidence has increased substantially in the last 10 years, and is the single leading cause of death for women ages 40-49 years in the United States. Suc...

Claims

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Application Information

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IPC IPC(8): A61K38/54A61K38/20A61K38/19A61K38/21A61K31/282A61K31/4745A61K31/337A61K31/704A61K33/24
CPCA61K31/337A61K45/06A61P35/00
Inventor GULATI, ANIL
Owner THE BOARD OF TRUSTEES OF THE UNIV OF ILLINOIS
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